1,720,963 research outputs found
Synthesis of Pharmaceutically Active Heterocycles and Lipid Targets: Novel Rearrangements and Methods for Carbon-Heteroatom Bond Formation
No full textThe pharmaceutical industry faces considerable challenges, not only from an R&D standpoint, but also politically and fiscally. Politically, governments around the world are trying to contain costs, and these costs are constantly the subject of intense scrutiny, with the real risk that the public health is suffering the consequences. Therefore, as scientists, we are called to innovate processes and help with witty and affordable solutions. In particular, as synthetic organic chemists, we are called to use imagination and expertise to bring new attractive organic transformations or bright improvements of existing processes, in order to maintain active and alive the real engine of innovation: research. Both from an academic and industrial point of view, new approaches for the achievement of synthetic fragments, moieties or targets are constantly required in a straightforward but brilliant fashion.\ud
For our part, we decided to investigate some of the most recurrent topics in organic chemistry and provide new synthetic ideas. This work has been divided into three main chapters, which incorporate topics such as the synthesis of biologically interesting lipid targets and pharmaceutically relevant heterocyclic structures. Therefore we put in place the search for new methods aimed at the formation of new carbon-carbon and carbon-heteroatom bonds. We addressed concerns about the quest for selectivity in the formation of these bonds, providing stereo-, chemo- and regioselective synthetic solutions. Specifically, the work described in Chapters 1 and 2 was carried out from January 2011 to January 2013 in the laboratories of Prof. Marcantoni at the University of Camerino, and focuses on the formation of new C-C and C-heteroatom bonds for the construction of more complex heterocyclic and lipid structures, mainly involving cerium (III) salts as Lewis acids and organometallic compounds. The results presented in the third chapter were achieved from February 2013 to December 2013 under the guidance of Dr. Jeremy T. Starr at Pfizer’s Worldwide Research & Development Center in Groton, Connecticut, USA. Chapter 3 was dedicated to the study and the development of new applications of a novel thermal rearrangement of propargyl amine N-oxides, powerful acyclic precursors for the achievement of more interesting heterocyclic structure. As a proof of the validity of the method, and given the particular interest of heterocycles in medicinal chemistry, synthesis of Celebrex®, a drug commercialized by Pfizer, was carried out.\ud
The author wishes to thank Prof. Enrico Marcantoni, for his guidance and for the valuable expertise continuously provided. All the people who have been part of the group over the years, for friendship and helpful discussions. Dr. Jeremy T. Starr for extraordinarily mentoring the author and for the warm welcome in his great and highly qualified group. My family and my dad for making me the person I am
Construction of heterocyclic structures by trivalent cerium salts promoted bond forming reactions
No full textCerium(III) salts have recently gained increasing attention in the synthetic community, owing to the powerful features that are reviewed in detail in this tutorial. This review reports significant examples of cerium(III) promoted synthesis of heterocyclic structures, initially dealing with the synthesis of five and six-membered ring nitrogen containing heterocycles, then describing the preparation of their oxygenated analogues and finally discussing the achievement of seven-membered rings and mixed heterocyclic motifs
Novel and efficient CeCl3.7H2O/NaI-catalyzed sulfenylation of indoles and pyrroles
No full textThe preparation and manipulation of functionalized low molecular weight heteroaromatic compounds is of increasing importance for obtaining new more potent pharmaceuticals. In particular, 3-sulfenyl indoles and 2-sulfenyl pyrrole are an important class of compounds due their activity towards the treatment of several deseases, and as inhibitors in medicinal chemistry. Most of methods for their preparation are based on electrophilic aromatic sulfenylation, but a considerable number of them have been unsatisfactory because the procedures provide low yields of the desired products, and/or require harsh conditions that are incompatible with sensitive functional groups [4]. In the framework of our ongoing program in the development of Lewis acid-catalyzed reactions by CeCl3 [5], we have developed a new general and efficient methodology for the sulfenylation of indoles and pyrroles by N-(alkylthio)- and N-(arylthio)phthalimides in the presence of our combination CeCl3.7H2O/NaI
An Efficient Catalytic Method for Regioselective Sulfenylation of Electron-rich Aza-aromatics at RoomTtemperature
Full text linkElectron-rich aza-aromatic compounds such as indoles and pyrroles represent systems of particular interest and importance in organic chemistry. An useful methodology for regioselective direct introduction of sulfenyl group on electron-rich aza-aromatics through S-alkyl and S-arylthiophthalimides as sulfenylating agents is described. Catalytic amounts of CeCl3.7H2O-NaI system are crucial to the promotion of this regioselective carbon-sulfur bond-forming Friedel-Crafts reaction. The reaction occurred in mild conditions and the products were obtained in good to excellent yields. Due to the large importance of functionalized indoles among natural compounds and pharmaceutical products, the methodology represents an efficient preparation of sulfenyl aza-aromatics, which are useful intermediates for important organic transformations
Isolation, characterization, and synthesis of degradation products of methylprednisolone derivatives
No full textCorticosteroids are important synthetically produced glucocorticoids used as anti-inflammatory drugs. Although the active pharmaceutical substances such as methylprednisolone derivatives have been on the market for many years, not much information is available in the literature regarding their degradation behaviors. During the course of our studies on polyfunctional molecules with biological activity, we have been interested in exploring the determination of possible degradation products of methylprednisolone hemisuccinate, and also their identification. These degradation products are interesting molecules from the pharmaceutical point of view, and are currently under biological evaluation. On the basis of fragmentation pathway and molecular weight obtained by LC-MS results, possible chemical structures can be proposed. Most of them are not sufficiently stable to be isolated, then only by synthesis it is possible to confirm the structures proposed by LC-MS results
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Efficient One-pot Catalyst in the Construction of 2-Substituted Benzimidazoles: Synthesis of Benzimidazo[1,2-c]quinazolines
No full textThe benzimidazole core is a common moiety in a large number of natural products and pharmacologically active small molecules. The synthesis of novel benzimidazole derivatives remains a main focus in medicinal research. In continuation of the efforts towards Ce(III) catalysts for organic transformations, we observed for the first time the activity of the iodide ion and copper cation in activating CeCl3·7H2O in the selective formation of prototypical 2-substituted benzimidazoles. The one-pot CeCl3·7H2O–CuI catalytic system procedure includes the cyclo-dehydrogenation of aniline Schiff’s bases, generated in situ from the condensation of 1,2-phenylenediamine and aldehydes, followed by the oxidation with iodine, which works as a hydrogen sponge. Mild reaction conditions, good to excellent yields, and clean reactions make the procedure a useful contribution to the synthesis of biologically active fused heterocycles containing benzimidazoquinazolines.
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